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Allogeneic ABCB5-positive Dermal Mesenchymal Stromal Cells for Treatment of CVU (Phase IIb)

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ClinicalTrials.gov Identifier: NCT04971161
Recruitment Status : Recruiting
First Posted : July 21, 2021
Last Update Posted : September 9, 2021
Sponsor:
Collaborators:
FGK Clinical Research GmbH
Ticeba GmbH
Information provided by (Responsible Party):
RHEACELL GmbH & Co. KG

Brief Summary:
The aim of this clinical trial is to investigate the efficacy (by monitoring the wound size reduction of CVUs) and safety (by monitoring adverse events [AEs]) of three dose groups of the investigational medicinal product (IMP) allo-APZ2-CVU, topically administered on target wounds of patients with CVU compared to placebo.

Condition or disease Intervention/treatment Phase
Skin Ulcer Venous Stasis Chronic Biological: allo-APZ2-CVU Drug: Placebo Phase 2

Detailed Description:

This is a randomized, placebo-controlled, double-blind, dose-ranging, multicenter, phase IIb clinical trial to investigate the efficacy and safety of the IMP allo-APZ2-CVU on wound healing in patients with therapy-resistant CVU. The allogeneic IMP allo-APZ2-CVU contains skin-derived ABCB5-positive dermal mesenchymal stromal cells isolated from skin tissue of healthy donors and stored in a donor cell bank.

Patients will be randomized to be treated with allo-APZ2-CVU (dose 1, dose 2, dose 3) or placebo (50 patients per dose group). The patients will undergo treatment with the IMP on Day 0 (V3) and will be followed up for efficacy for 18 weeks (V4 until V14). Two safety follow-up visits will be performed at Month 6 (V15) and Month 10 (V16).

The wound healing process will be documented by standardized photography. The wound size measurement will start at the first Screening Visit (V1) and will be measured at each following on-site visit.

Pain will be assessed using a numerical rating scale and quality of life will be investigated with standardized and validated questionnaires.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 200 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Randomized, placebo-controlled, double-blind, dose-ranging, interventional, multicenter, phase IIb clinical trial
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Randomized, Placebo-Controlled, Double-blind, Dose-Ranging, Multicenter, Phase IIb Clinical Trial to Investigate the Efficacy and Safety of Allo-APZ2-CVU on Wound Healing of Therapy-Resistant Chronic Venous Ulcer (CVU)
Actual Study Start Date : August 18, 2021
Estimated Primary Completion Date : August 2023
Estimated Study Completion Date : August 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: allo-APZ2-CVU (dose group 1: 1 x 10e6 cells/cm²)
Application of IMP on patients wound
Biological: allo-APZ2-CVU
Suspension of ABCB5-positive dermal mesenchymal stromal cells. One topical application with a syringe.
Other Name: Skin-derived ABCB5-positive dermal mesenchymal stromal cells

Placebo Comparator: Placebo
Application of IMP on patients wound
Drug: Placebo
One topical application with a syringe

Experimental: allo-APZ2-CVU (dose group 2: 3 x 10e6 cells/cm²)
Application of IMP on patients wound
Biological: allo-APZ2-CVU
Suspension of ABCB5-positive dermal mesenchymal stromal cells. One topical application with a syringe.
Other Name: Skin-derived ABCB5-positive dermal mesenchymal stromal cells

Experimental: allo-APZ2-CVU (dose group 3: 6 x 10e6 cells/cm²)
Application of IMP on patients wound
Biological: allo-APZ2-CVU
Suspension of ABCB5-positive dermal mesenchymal stromal cells. One topical application with a syringe.
Other Name: Skin-derived ABCB5-positive dermal mesenchymal stromal cells




Primary Outcome Measures :
  1. Complete wound closure at Week 18 already persisting for at least two weeks [ Time Frame: Week 18 ]
    Complete wound closure at Week 18 already persisting for at least two weeks will be evaluated.

  2. Assessment of adverse event (AE) occurrence [ Time Frame: Up to 10 months ]
    All AEs occurring during the clinical trial will be registered, documented and evaluated.


Secondary Outcome Measures :
  1. Wound size change in percent at each post-baseline follow-up visit [ Time Frame: Day 1-2, Week 1, 2, 4, 6, 8, 10, 12, 14, 16, Month 6 and 10 ]
    Wound size change in percent at each post-baseline follow-up visit will be evaluated.

  2. Time to complete wound closure [ Time Frame: Day 1-2, Week 1, 2, 4, 6, 8, 10, 12, 14, 16, Month 6 and 10 ]
    Time to complete wound closure will be evaluated.

  3. Complete wound closures at each post-baseline follow-up visit [ Time Frame: Day 1-2, Week 1, 2, 4, 6, 8, 10, 12, 14, 16, Month 6 and 10 ]
    Complete wound closures at each post-baseline follow-up visit will be evaluated.

  4. Duration of wound closure [ Time Frame: Day 1-2, Week 1, 2, 4, 6, 8, 10, 12, 14, 16, Month 6 and 10 ]
    Duration of wound closure will be evaluated.

  5. Recurrence of the wound [ Time Frame: Day 1-2, Week 1, 2, 4, 6, 8, 10, 12, 14, 16, Month 6 and 10 ]
    Recurrence of the wound will be evaluated.

  6. Quality of wound healing (wound exudate) at each post-baseline follow-up visit [ Time Frame: Day 1-2, Week 1, 2, 4, 6, 8, 10, 12, 14, 16, Month 6 and 10 ]
    The Quality of wound healing will be assessed at each post-baseline follow-up visit on the basis of the amount and type of wound exudate.

  7. Quality of wound healing (granulation tissue together with epithelialization) at each post-baseline follow-up visit [ Time Frame: Day 1-2, Week 1, 2, 4, 6, 8, 10, 12, 14, 16, Month 6 and 10 ]
    The Quality of wound healing will be assessed at each post-baseline follow-up visit on the basis of the formation of granulation tissue together with epithelialization.

  8. Quality of wound healing (scar formation) at each post-baseline follow-up visit [ Time Frame: Day 1-2, Week 1, 2, 4, 6, 8, 10, 12, 14, 16, Month 6 and 10 ]
    The Quality of wound healing will be assessed at each post-baseline follow-up visit on the basis of the questions regarding scar formation.

  9. Assessment of Quality of Life using the Wound-Quality of Life Questionnaire at V8, V11, V14 [ Time Frame: Week 6, 12, 18 ]
    Quality of Life using the Wound-Quality of Life Questionnaire at V8, V11, V14 will be evaluated.

  10. Pain assessment as per numerical rating scale on each post-baseline efficacy follow-up visit [ Time Frame: Day 1-2, Week 1, 2, 4, 6, 8, 10, 12, 14, 16, Month 6 and 10 ]
    Pain assessment as per numerical rating scale on each post-baseline efficacy follow-up visit will be evaluated.

  11. Physical examination and vital signs at V14 [ Time Frame: Week 18 ]
    A physical body examination (e.g. general appearance, thyroid, head, lungs and thorax, ears, cardiovascular system, eyes, abdomen, nose-mouth-throat, musculoskeletal system, skin, extremities, lymph nodes, neurological system) will be performed and abnormal physical examination results will be evaluated and reported as AEs.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male or female patients at least 18 years old;
  2. Chronic venous leg ulcer (as defined by the current AWMF guidelines: therapy-resistant ulcer that shows no tendency to heal within 3 months despite of optimal phlebological therapies or has not fully healed within 12 months) at lower leg and/or ankle region and has not been present longer than 15 years, diagnosed by doppler or duplex sonography, ankle brachial index (ABI, 0.9-1.3), physical examination and dermatological review;
  3. Wound size of target ulcer between 1 and 50 cm² measured by a standardized photography at the screening visits (Visit 1 and Visit 2);
  4. If patients have 2 or more ulcers at the same extremity, the target ulcer has to be separated by a minimum bridge of 1 cm of epithelialized skin from other ulcers (the largest ulcer should be the target ulcer, if not decided otherwise at discretion of the investigator; the target ulcer is defined at Visit 1);
  5. Body mass index between 15 and 50 kg/m²;
  6. Patients understand the nature of the procedure and are providing written informed consent prior to any clinical trial procedure;
  7. Women of childbearing potential must have a negative blood pregnancy test at Visit 1;
  8. Women of childbearing potential and their partner must be willing to use highly effective contraceptive methods during the course of the clinical trial.

Exclusion Criteria:

  1. Evidence of the ulcer extending to the underlying muscle, tendon, or bone;
  2. Diabetes mellitus that has to be confirmed by blood test (Hemoglobin A1c >7.5%);
  3. Peripheral Artery Disease including claudication with need of treatment;
  4. Acute deep vein thrombosis (maximum 30 days from diagnosis) or a still untreated deep vein thrombosis;
  5. Unable to tolerate leg ulcer compression bandage;
  6. Infection of the target ulcer requiring treatment as judged clinically;
  7. All diagnosed disorders, unrelated to CVU, that are influencing wound healing of the target wound at investigator's discretion;
  8. Current use of medications that influence wound healing: systemic immunosuppressives, cytotoxic medicinal products, and systemic steroids (above Cushing-threshold level);
  9. Patient who, in the opinion of the investigator, for any reason are unable or unwilling to complete the trial per protocol (e.g. alcohol or substance abuse, not mobile, short life expectancy) or there is evidence of any other medical condition (such as psychiatric illness, physical examination, or laboratory findings) that may interfere with the planned treatment, affect the patient's compliance, or place the patient at high risk of complications related to the treatment;
  10. Any malignancy within the past 5 years, excluding successfully treated carcinoma in situ, basal cell carcinoma or squamous cell carcinoma of the skin without evidence of metastases;
  11. Pregnant or lactating women;
  12. Any known allergies to components of the IMP;
  13. Prior surgical procedures such as bypass or mesh-graft treatment at target leg within 2 months prior to Visit 1 at target leg;
  14. Patients with significant ulcer healing or wound size enlargement of more than 25% at Visit 2 compared to Visit 1;
  15. Treatment of target ulcer with active wound care agents (e.g. Iruxol®N, silver dressings), which have not been paused 14 days before IMP application;
  16. Current or previous (within 30 days of enrollment) treatment with another IMP, or participation and/or under follow-up in another clinical trial;
  17. Previous participation in this clinical trial (except for screening failures due to an inclusion or exclusion criterion);
  18. Employees of the sponsor, or employees or relatives of the investigator.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04971161


Contacts
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Contact: Christoph Ganss, Dr. +49 6221 71833 ext 0 office@rheacell.com
Contact: Anna Mößmer +49 6221 71833 ext 0 anna.moessmer@rheacell.com

Locations
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Sponsors and Collaborators
RHEACELL GmbH & Co. KG
FGK Clinical Research GmbH
Ticeba GmbH
Investigators
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Principal Investigator: Andreas Kerstan, Dr. Klinik und Poliklinik für Dermatologie, Venerologie und Allergologie, Würzburg
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Responsible Party: RHEACELL GmbH & Co. KG
ClinicalTrials.gov Identifier: NCT04971161    
Other Study ID Numbers: allo-APZ2-CVU-IIb
First Posted: July 21, 2021    Key Record Dates
Last Update Posted: September 9, 2021
Last Verified: September 2021

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by RHEACELL GmbH & Co. KG:
Chronic Venous Ulcer
ABCB5
Allogeneic
Dermal mesenchymal stromal cells
varicose ulcer
skin ulcer
advanced therapy medicinal product
somatic cell therapy
phase IIb
Additional relevant MeSH terms:
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Varicose Ulcer
Skin Ulcer
Ulcer
Pathologic Processes
Varicose Veins
Vascular Diseases
Cardiovascular Diseases
Leg Ulcer
Skin Diseases